-
Paul Hebeisen,
Wolfgang Haap,
Bernd Kuhn,
Peter Mohr, Hans Peter Wessel,
Ulrich Zutter,
Stephan Kirchner,
Armin Ruf,
Jörg Benz,
Catherine Joseph,
Rubén Alvarez-Sánchez,
Marcel Gubler,
Brigitte Schott,
Agnes Benardeau,
Effie Tozzo,
Eric Kitas
[show abstract]
[hide abstract]
ABSTRACT: A novel sulfonylureido pyridine series exemplified by compound 19 yielded potent inhibitors of FBPase showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes. Our inhibitors occupy the allosteric binding site and also extend into the dyad interface region of tetrameric FBPase.
Bioorganic & medicinal chemistry letters 06/2011; 21(11):3237-42. · 2.65 Impact Factor
-
Markus Boehringer,
Holger Fischer,
Michael Hennig,
Daniel Hunziker,
Joerg Huwyler,
Bernd Kuhn,
Bernd M Loeffler,
Thomas Luebbers,
Patrizio Mattei,
Robert Narquizian,
Elena Sebokova,
Urs Sprecher, Hans Peter Wessel
[show abstract]
[hide abstract]
ABSTRACT: Synthesis and SAR are described for a structurally distinct class of DPP-IV inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.
Bioorganic & medicinal chemistry letters 02/2010; 20(3):1106-8. · 2.65 Impact Factor
-
Eric Kitas,
Peter Mohr,
Bernd Kuhn,
Paul Hebeisen, Hans Peter Wessel,
Wolfgang Haap,
Armin Ruf,
Jörg Benz,
Catherine Joseph,
Walter Huber,
Ruben Alvarez Sanchez,
Axel Paehler,
Agnes Benardeau,
Marcel Gubler,
Brigitte Schott,
Effie Tozzo
[show abstract]
[hide abstract]
ABSTRACT: Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure-activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes.
Bioorganic & medicinal chemistry letters 11/2009; 20(2):594-9. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tetrakis(dimethylamino)ethylene (TDAE 1 ), has been exploited for the first time as a mild reagent for the reduction of arenediazonium salts to aryl radical intermediates through a single electron transfer (SET) pathway. Cyclization of the aryl radicals produced in this way led, in appropriate substrates, to syntheses of indolines and indoles. Cascade radical cyclizations of aryl radicals derived from arenediazonium salts are also reported. The relative ease of removal of the oxidized by-products of TDAE from the reaction mixture makes the methodology synthetically attractive.
Beilstein Journal of Organic Chemistry. 01/2009;
-
Thomas Lübbers,
Markus Böhringer,
Luca Gobbi,
Michael Hennig,
Daniel Hunziker,
Bernd Kuhn,
Bernd Löffler,
Patrizio Mattei,
Robert Narquizian,
Jens-Uwe Peters,
Yves Ruff, Hans Peter Wessel,
Pierre Wyss
[show abstract]
[hide abstract]
ABSTRACT: In a search for novel DPP-IV inhibitors, 2-aminobenzo[a]quinolizines were identified as submicromolar HTS hits. Due to the difficult synthetic access to this compound class, 1,3-disubstituted 4-aminopiperidines were used as model compounds for optimization. The developed synthetic methodology and the SAR could be transferred to the 2-aminobenzo[a]quinolizine series, leading to highly active DPP-IV inhibitors.
Bioorganic & Medicinal Chemistry Letters 07/2007; 17(11):2966-70. · 2.55 Impact Factor
-
Katrin Groebke Zbinden,
Ulrike Obst-Sander,
Kurt Hilpert,
Holger Kühne,
David W Banner,
Hans-Joachim Böhm,
Martin Stahl,
Jean Ackermann,
Leo Alig,
Lutz Weber, Hans Peter Wessel,
Markus A Riederer,
Thomas B Tschopp,
Thierry Lavé
[show abstract]
[hide abstract]
ABSTRACT: We describe the structure-based design and synthesis of highly potent, orally bioavailable tissue factor/factor VIIa inhibitors which interfere with the coagulation cascade by selective inhibition of the extrinsic pathway.
Bioorganic & Medicinal Chemistry Letters 01/2006; 15(23):5344-52. · 2.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: [reaction: see text] A novel, mild, ecofriendly protocol for the deoxygenation of epoxides to alkenes using indium metal and indium(I) chloride or ammonium chloride in alcohol has been developed. It was necessary for the presence of good radical-stabilizing groups adjacent to the oxirane ring for the deoxygenation reaction to occur. It is proposed that this reaction occurs through an SET process with indium as an electron donor.
The Journal of Organic Chemistry 06/2005; 70(10):4118-23. · 4.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The first examples of highly enantioselective [2,3]-sigmatropic rearrangements of acyclic allylic ammonium ylids are reported. Thus, a range of N-{2'-[(N'-allyl-N',N'-dialkyl)ammonium]}acetyl camphor sultams undergo rearrangement at 0 degrees C in DME solution with high diastereofacial control (up to 99:1 dr) to give allylglycines in generally high yield. The power of the method has been demonstrated in a rapid and efficient synthesis of (R)-allyl glycine.
Journal of the American Chemical Society 03/2005; 127(4):1066-7. · 9.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A ring-contractive and highly diastereoselective [2,3]-sigmatropic rearrangement occurs when N-methyl-1,2,3,6-tetrahydropyridine is treated with sub-stoichiometric amounts of copper or rhodium salts, in the presence of ethyl diazoacetate, giving ethyl cis-N-methyl-3-ethenyl proline (4).
The Journal of Organic Chemistry 06/2003; 68(10):4083-6. · 4.45 Impact Factor
-
Journal of Carbohydrate Chemistry 09/1996; 15(7):769-786. · 0.63 Impact Factor
-
Journal of Carbohydrate Chemistry. 04/1992; 11(3):255-263.
-
Bioorganic & Medicinal Chemistry Letters. 5(5):437-442.
-
Bioorganic & Medicinal Chemistry Letters. 6(1):27-32.
-
Thomas Luebbers,
Markus Boehringer,
Luca Gobbi,
Michael Hennig,
Daniel Hunziker,
Bernd Kuhn,
Bernd Loeffler,
Patrizio Mattei,
Robert Narquizian,
Jens-Uwe Peters,
Yves Ruff, Hans Peter Wessel,
Pierre Wyss
[show abstract]
[hide abstract]
ABSTRACT: In a search for novel DPP-IV inhibitors, 2-aminobenzo[a]quinolizines were identified as submicromolar HTS hits. Due to the difficult synthetic access to this compd. class, 1,3-disubstituted 4-aminopiperidines were used as model compds. for optimization. The developed synthetic methodol. and the SAR could be transferred to the 2-aminobenzo[a]quinolizine series, leading to highly active DPP-IV inhibitors I. [on SciFinder(R)]
Bioorg. Med. Chem. Lett. FIELD Full Journal Title:Bioorganic & Medicinal Chemistry Letters. 17(11):2966-2970.
